Fraxin Alleviates LPS-Induced ARDS by Downregulating Inflammatory Responses and Oxidative Damages and Reducing Pulmonary Vascular Permeability

Inflammation. 2019 Oct;42(5):1901-1912. doi: 10.1007/s10753-019-01052-8.


Acute respiratory distress syndrome (ARDS) is a severe acute disease that threatens human health, and few drugs that can effectively treat this disease are available. Fraxin, one of the main active ingredients of Cortex Fraxini, a Chinese herbal medicine, has presented various pharmacological and biological activities. However, the effects of fraxin on ARDS have yet to be reported. In the present study, the protective effect of fraxin in lipopolysaccharide (LPS)-induced ARDS in a mouse model was analyzed. Results from the hematoxylin and eosin staining showed that fraxin might alleviate pathological changes in the lung tissues of mice with ARDS. ELISA and Western blot results revealed that fraxin might inhibit the production of inflammatory factors, namely, IL-6, TNF-α, and IL-1β, and the activation of NF-κB and MAPK signaling pathways in the lungs. Thus, the inflammatory responses were reduced. Fraxin might inhibit the increase in reactive oxygen species (ROS) and malondialdehyde (MDA), a product of lipid peroxidation in lung tissues. Fraxin might increase the superoxide dismutase (SOD) activity to avoid oxidative damage. Vascular permeability was also assessed through Evans blue dye tissue extravasation and fluorescein isothiocyanate-labeled albumin (FITC-albumin) leakage. Fraxin might inhibit the increase in pulmonary vascular permeability and relieve pulmonary edema. Fraxin was also related to the inhibition of the increase in matrix metalloproteinase-9, which is a glycocalyx-degrading enzyme, and the relief of damages to the endothelial glycocalyx. Thus, fraxin elicited protective effects on mice with LPS-induced ARDS and might be used as a drug to cure ARDS induced by Gram-negative bacterial infection.

Keywords: ARDS; fraxin; inflammatory responses; lipopolysaccharide; oxidative damages; pulmonary vascular permeability.

MeSH terms

  • Animals
  • Capillary Permeability / drug effects
  • Coumarins / pharmacology*
  • Coumarins / therapeutic use
  • Down-Regulation
  • Glycocalyx / metabolism
  • Inflammation / drug therapy
  • Lipopolysaccharides
  • Lung / drug effects
  • Lung / pathology
  • MAP Kinase Signaling System / drug effects
  • Mice
  • NF-kappa B / metabolism
  • Oxidation-Reduction / drug effects
  • Respiratory Distress Syndrome / drug therapy
  • Respiratory Distress Syndrome / prevention & control*


  • Coumarins
  • Lipopolysaccharides
  • NF-kappa B
  • fraxin